Z-cyclohexyl and z-cyclohexylidene



Patented Mar. 25, 1952 Z-CYCLOHEXYL AND 2-CYCLOHEXYLIDENE- 1-(3- PIPERIDINO PROPYL) CYCLOHEX- AN OLS Karl Miescher, Riehen, and Adrian Marxer, Basel, Switzerland, assignors to Ciba Pharmaceutical Products, Inc., Summit, N. J.

No Drawing. Application December 27, 1950, Se-

rial No. 203,022. In Switzerland February 1,

1 Claim. (Cl. 260-294.7)

The present invention is for the manufacture of 2-cyclohexylideneand 2-cyc10hexyl-1-(3 piperidino-propyl) -cyclohexanol of the formulae and.

respectively, and salts thereof.

These new compounds are powerful spasmolytics, and as compared with comparable known compounds they are especially active against Parkinsons disease. They are useful as medicaments.

The aforesaid cyclohexanols are obtained by reacting an N -[1-halogen-propyl-(3) l-piperidine with a metal and then with 2-cyclohexylidenecyclohexanone or 2 cyclohexyl cyclohexanone, and if desired hydrogenating the resulting 2- cyclohexylidene 1 (3' piperidino propyD- cyclohexanol. As metals there may be used primarily magnesium, yet also cadmium or zinc are suitable. In the reaction, for example with magnesium, the corresponding organometal compound is formed and then the latter reacts with the above mentioned cyclohexanones. It is of advantage to activate the metal; thus, for example, magnesium may be activated with the aid of a small quantity of iodine and/or an alkyl halide.

By the process of the invention metal compounds of the above cyclohexanols are obtained which may be converted into the free cyclohexanols for example, by reaction with a mineral acid. In this way the usual salts of the bases are obtained, from which salts the free bases can be obtained in the usual manner. From the free bases salts can be prepared with acids such, for example as hydrohalic acids, sulfuric acid, nitric acid, phosphoric acid, thiocyanic acid, acetic acid, propionic acid, oxalic acid, malic acid, citric acid, benzoic acid, methane sulfonic acid, ethane sulf-onic acid, oXy-ethane sulfonic acid, benzene sulfonic acid or toluene sulfonic acid.

The following examples illustrate the inven- 2 tion, the parts being by weight unless otherwise stated and the relationship of parts by weight to parts by volume being the same as that of the gram to the cubic centimeter:

Example 1 12.0 parts of magnesium are covered with a small quantity of absolute ether. Ethyl bromide is added to initiate the reaction, and then 46.8 parts of N-[l-chloropropyl-(3) l-piperidine in parts by volume of absolute benzene and 75 parts by volume of absolute ether are added rather quickly while stirring and gently heating. After stirring for 4 hours in a water bath at C., 42.8 parts of 2-cyclohexylidene-cyclohexanone are added in small portions and the reaction mixture is maintained for a further 5 hours at 50 C. The reaction product is then mixed with dilute hydrochloric acid, whereupon the crystalline, sparingly soluble hydrochloride of 2-cyclohexyl idene 1 (3'-piperidino-propyl) cyclohexanol of the formula precipitates from the hydrochloric acid solution. After recrystallisation from a mixture of alcohol and ethyl acetate it melts at 223-225" C. By agitating the hydrochloride with ether and potassium carbonate there can be obtained the free base which boils at 146-148 C. under 0.07 mm. pressure.

Example 2 CHzCHzCHzN Example 3 The procedure is the same as that described in Example 1, except that, instead of the 2- cyclohexylidene-cyclohexanone, 43.0 parts of 2- cyclohexyl cyclohexanone are used. The 2- cyclohexyl 1 (3' piperidino propyl) cyclohexanol described in Example 2 is obtained.

What is claimed is:

A member selected from the group consisting 4 and 2 cyclohexyl 1 (3' piperidino propy1)- cyclohexanol of the formula HO omomcmN KARL MIESCHER. ADRIAN MARXER.

REFERENCES CITED of 2 cyclohexylidene -1- (3'-piperidino-propy1) 15 The following-references are of record in the cyclohexanol of the formula I HO CHzCH CHgN G file of this patent:

FOREIGN PATENTS Number Country Date 234,931 Switzerland Mar. 1, 1945 234,932 Switzerland Mar. 1, 1945 

